The ultimate goal of our investigation is to control Diabetes Mellitus in human by fetal pancreas transplants. The immediate goal of the proposed investigation is to demonstrate the reversal of streptozotocin-induced diabetes in rats by fetal pancreas allografts by induction of specific unresponsiveness. Our current study with allografts across weak, non-H-1 incompatibilities(LEW-F344) has demonstrated complete and permanent (more than 1 year) reversal of diabetes in 85% recipients and complete but transient reversal (50-70 days) in the remaining recipients using pretreatment of donor antigens and a single injection of each procarbazin hydrocloride and ALA within few days of transplantation. With similar treatments fetal pancreas allograft survivals in stronger incompatibilities prolonged 4-5 times of the control survival times. The proposed study will: (1) attempt induction of long lasting unresponsiveness to donor fetal pancreases in combinations across intermediate(F344-LEW) and stong (BUF - LEW) incompatibilities by improvement of the treatment, (2) clarify the mechanisms of the supression, confirm specificity, and test host immune response to other antigens, diabetes-reversed recipients with fetal pancreas isografts or allografts, and (4) examine the fate of transplants under two immune state, immunity against insulin and/or islets elements.